Protective effects of exercise training on emotional and cognitive dysfunction in Alzheimer's disease mice:the involvement of NLRP3 mediated microglial pyroptosis
10.3969/j.issn.1001-1242.2025.09.002
- VernacularTitle:运动训练抑制NLRP3介导的小胶质细胞焦亡改善阿尔茨海默病小鼠焦虑样行为和认知障碍的作用与机制研究
- Author:
Lili LI
1
;
Mingyue LI
1
;
Xiaofei HE
1
Author Information
1. 中山大学附属第三医院康复医学科,广东省 广州市,510630
- Publication Type:Journal Article
- Keywords:
Alzheimer's disease;
cognitive rehabilitation;
physical exercise;
microglia;
pyroptosis;
NLRP3
- From:
Chinese Journal of Rehabilitation Medicine
2025;40(9):1298-1307
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protective effect of exercise training on emotional and cognitive dysfunction in Alzheimer's disease(AD),as well as the involvement of NLRP3 mediated microglial pyroptosis.Method:Male 5xFAD mice at the age of 5 months were randomly divided into control and physical exer-cise,(PE)groups.Age-matched C57/BL6 mice were used as wild type(WT)group.The mice in the WT and the control groups were fed in a common cage,while the mice in the PE group were fed in a cage equipped with a running wheel,in which mice were freely to run.Open field test was used to detect the emo-tional function,the Morris water maze test was used to detect the spatial cognitive function,and immunofluo-rescence staining was used to detect the neuronal survival,Amyloid beta(Aβ)plaque deposition,the microgli-al activation,the aggregation of microglial lysosomes and the expression of GSDMD,which is related to py-roptosis.The expression of inflammatory cytokines、proinflammatory cytokines and GSDMD protein were detect-ed by Western Blots.Result:In open field test,when comparing with WT group,the time spent in the central area was significant-ly shortened in the control-5xFAD group,which was significantly extended in the PE-5xFAD group.During the Morris water maze training period,the latencies of mice in the WT and PE-5xFAD groups to the platform were gradually decreased,while there was no significant differences in the control-5xFAD group.During the probe trial test,the times crossing the platform in the control-5xFAD group was significantly reduced compared with that in the WT group,while which was significantly increased in the PE-5xFAD mice.The number of neurons in the PE-5xFAD group was significantly increased in cortex and hippocampus compared with those in the control-5xFAD group,while Aβ1-42 plaques were significantly decreased in the PE-5xFAD group.Com-pared with the WT group.In addition,the lysosomal associated membrane protein-1(Lamp1)was obviously de-tected around the Aβ plaques in the control-5xFAD group.However,physical exercise significantly reduced the expressions of Lamp1 and CtsB in the cortex and hippocampus of 5xFAD mice.In the control-5xFAD group,the proinflammatory cytokines were significantly increased in cortex and hippocampus when compared with the WT mice,while PE decreased the expression of proinflammatory cytokines and increased the expression of anti-inflammatory cytokine.When compared with the WT mice,the 5xFAD mice exhibited a significantly increased expression of GSDMD protein in cortex and hippocampus,while PE decreased the expression of GSDMD pro-tein.Moreover,GSDMD protein was co-localized with Iba-1-positive microglia.Conclusion:Physical exercise improves cognitive function in Alzheimer's disease by inhibiting NLRP3-mediat-ed microglial pyroptosis.
